Since the longevity of women exceeds that of men, chronic, high dose estrogen therapy is commonly prescribed following the menopause on the assumption that premenopausal ovarian function is the mechanism for this differential. However, studies of long-term estrogen therapy in men have actually led to increased cardiovascular mortality. The resolution of this paradox is the goal of the proposed research, which will investigate the effects of pharmacological estrogen therapy on 3 phenomena related to vascular disease: 1) The degree and mechanism of the hyperlipidemia induced; 2) Effects, direct and indirect, on arterial smooth muscle cell proliferation in culture; and 3) Effects on thrombosis, thrombolysis, and platelet turnover. The first will be both epidemiological (through special analysis of data being collected in a large survey of an adult employee population under the auspices of the Northwest Lipid Research Clinic) and clinical investigations, studying effects of estrogen upon triglyceride turnover, adipose tissue and post-heparin triglyceride lipase, insulin secretion, and lipids, lipoproteins, and apolipoproteins in paired studies of normo- and hyperlipidemic volunteers. The second will assess effects of estrogen and estrogen-induced serum changes upon the proliferative response of monkey aorta smooth muscle cells in culture. And the last will assess thrombokinetics and in vitro platelet function in both normo- and hyperlipidemic volunteers before and during estrogen therapy.